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(TRAIL)-Mediated Apoptosis by Helicobacter Pylori in Immun

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(TRAIL)-Mediated Apoptosis by Helicobacter Pylori in Immun + MODEL Journal of Microbiology, Immunology and Infection (2016) xx,1e6 Available online at www.sciencedirect.com ScienceDirect journal homepage: www.e-jmii.com REVIEW ARTICLE Modulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis by Helicobacter pylori in immune pathogenesis of gastric mucosal damage Hwei-Fang Tsai a,b, Ping-Ning Hsu c,d,* a Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, Taipei, Taiwan b Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan c Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan d Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Received 1 March 2015; received in revised form 20 December 2015; accepted 17 January 2016 Available online --- KEYWORDS Abstract Helicobacter pylori infection is associated with chronic gastritis, peptic ulcer, apoptosis; gastric carcinoma, and gastric mucosa-associated lymphoid tissue lymphomas. Apoptosis chemokine; induced by microbial infections is implicated in the pathogenesis of H. pylori infection. FLIP; Enhanced gastric epithelial cell apoptosis during H. pylori infection was suggested to play Helicobacter pylori; an important role in the pathogenesis of chronic gastritis and gastric pathology. In addition TRAIL to directly triggering apoptosis, H. pylori induces sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in gastric epithelial cells. Human gastric epithelial cells sensitized to H. pylori confer susceptibility to TRAIL-mediated apoptosis via modulation of death-receptor signaling. The induction of TRAIL sensitivity by H. pylori is dependent upon the activation of caspase-8 and its downstream pathway. H. pylori induces caspase-8 activation via enhanced assembly of the TRAIL death-inducing signaling complex through downregulation of cellular FLICE-inhibitory protein. Moreover, H. pylori infection in- duces infiltration of T lymphocytes and triggers inflammation to augment apoptosis. In H. py- lori infection, significant increases in CCR6þ CD3þ T cell infiltration in the gastric mucosa was observed, and the CCR6 ligand, CCL20 chemokine, was selectively expressed in inflamed gastric tissues. These mechanisms initiate chemokine-mediated T lymphocyte trafficking into inflamed epithelium and induce mucosal injury during Helicobacter infection. This article will review recent findings on the interactions of H. pylori with host-epithelial signaling pathways and events involved in the initiation of gastric pathology, including gastric inflammation and mucosal damage. * Corresponding author. Graduate Institute of Immunology, College of Medicine, National Taiwan University, 1 Jen-Ai Road, Section 1, Taipei 100, Taiwan. E-mail address: [email protected] (P.-N. Hsu). http://dx.doi.org/10.1016/j.jmii.2016.01.002 1684-1182/Copyright ª 2016, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Tsai H-F, Hsu P-N, Modulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)- mediated apoptosis by Helicobacter pylori in immune pathogenesis of gastric mucosal damage, Journal of Microbiology, Immunology and Infection (2016), http://dx.doi.org/10.1016/j.jmii.2016.01.002 + MODEL 2 H.-F. Tsai, P.-N. Hsu Copyright ª 2016, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). Helicobacter pylori infection and apoptosis in homology with FasL that is capable of inducing apoptosis in 22,23 gastric epithelial cells a variety of transformed cell lines in vitro, but usually not in normal primary cells. T cells can kill target cells via TRAIL/TRAIL-receptor interaction,24,25 indicating that Helicobacter pylori is a common human pathogen that in- TRAIL might serve as a cytotoxic effector molecule in fects over half of the world population and is associated activated T cells in vivo. These findings suggested that with duodenal and peptic ulcer diseases. The clinical con- TRAIL/TRAIL-receptor interaction is involved in the inter- sequences range from asymptomatic gastritis to peptic ul- action between infiltrating T cells and gastric epithelium ceration and gastric malignancy.1,2 The outcome of the during H. pylori gastritis. Recent studies demonstrated that infection is determined by interactions among H. pylori human gastric epithelial cells sensitized to H. pylori confer virulence factors, host gastric mucosal factors, and the susceptibility to TRAIL-mediated apoptosis, suggesting a environment. However, the mechanisms by which host role for immune-mediated apoptosis in gastric epithelial factors cause disease remain unclear. Apoptosis induced by cells by infiltrating T cells during Helicobacter infec- microbial infections is implicated in the pathogenesis of H. tion.6,14,26 The induction of TRAIL sensitivity by H. pylori is pylori infection, and enhanced gastric epithelial cell dependent upon bacterial cell contact, irrespective of apoptosis during H. pylori infection was suggested to play expression of H. pylori virulent factors.6 an important role in the pathogenesis of chronic gastritis e TRAIL-induced apoptosis occurs through a caspase and gastric pathology.3 7 Direct cytotoxicity, as well as signaling cascade, and resistance to TRAIL is controlled by inflammatory responses, occurs in gastric mucosa e intracellular regulators of apoptosis. Crosslinking of the cells.5,8 10 H. pylori vacuolating (VacA) toxin induces TRAIL receptors leads to the formation of a death-inducing gastric epithelial cell apoptosis, but cytotoxin-associated signaling complex (DISC)27 assembled by the death-adaptor gene A (CagA) attenuates apoptosis in gastric epithelial protein Fas-associated death-domain protein (FADD) and cells. Bacterial virulent factors may contribute directly to e caspase-8 and -10.28 30 Activated caspase-8 is generated apoptosis in epithelial cells, whereas the induction of after DISC formation, and initiates apoptosis-inducing cas- sensitivity to death-receptor mediated apoptosis by H. py- pase signaling cascade. Previous studies demonstrated that lori is independent of H. pylori virulent factors VacA and TRAIL-induced apoptosis could be enhanced by Heli- CagA,6 suggesting that immune factors, in addition to cobacter and hepatitis C virus core proteins6,31; however, bacterial factors, are also important in determining the the mechanisms leading to microbe-induced TRAIL sensi- degree of gastric mucosa damage during H. pylori infection. tivity remain unclear. H. pylori-induced sensitivity to It was demonstrated that T helper type 1 (Th1) cells e TRAIL-mediated apoptosis in gastric epithelial cells is selectively increased during H. pylori infection.11 14 Th1 cy- dependent upon activation of the caspase-8 downstream tokines, such as interferon gamma (IFN-g) and tumor necrosis pathway for conveyance of death signals to mitochondria, factor alpha (TNF-a), can increase the release of proin- resulting in activation of mitochondrial pathways and flammatory cytokines, augmenting apoptosis induced by H. removing resistance to apoptosis. H. pylori also induces pylori.10 H. pylori infection could also induce gastric mucosa sensitivity to TRAIL-mediated apoptosis by regulation of damage by increasing expression of Fas in gastric epithelial FLICE-inhibitory protein (FLIP) and assembly of DISC, which cells, leading to gastric epithelial cell apoptosis through Fas/ initiates caspase activation26 and promotes apoptosis, Fas ligand (FasL) interaction with infiltrating T cells.9,15 These thereby providing insight into the pathogenesis of gastric findings suggest a role for immune-mediated apoptosis of damage during Helicobacter infection (Figure 1). Modula- gastric epithelial cells during H. pylori infection. Additionally, tion of host-cell apoptosis by bacterial interaction adds a H. pylori directly triggers cell death by cytotoxins after new dimension to immune pathogenesis associated with interacting with gastric epithelial cells.16,17 Furthermore, H. Helicobacter infection. pylori translocates CagA into gastric epithelial cells by Type IV secretion, inducing intracellular protein phosphorylation and dysregulating signal transduction pathways within host cells.18e21 In addition to directly triggering apoptosis, it is Chemokine-mediated lymphocyte trafficking possible that H. pylori induces sensitivity to apoptosis in of T lymphocytes in gastric inflammation gastric epithelial cells via modulation of apoptosis signaling. during H. pylori infection H. pylori modulate tumor necrosis factor- During H. pylori infection, the degree of apoptosis induced in the stomach is affected by the inflammatory response. H. related apoptosis-inducing ligand (TRAIL)- pylori infection induces a T cell response, as well as a mediated apoptosis in gastric epithelial cells number of inflammatory mediators, including cytokines and chemokines.7,11,14,32 These infiltrating T cells can then TNF-related apoptosis-inducing ligand (TRAIL; also called target and destroy gastric cells via TRAIL/TRAIL-receptor Apo2L) is a novel TNF superfamily member with strong interaction. In addition to its role in inducing apoptosis by Please cite this article in press as: Tsai H-F, Hsu P-N, Modulation of
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